Insight into the catalytic mechanism of thymidylate synthase ThyX of Campylobacter jejuni

Abstract : For de novo synthesis of the essential DNA precursor dTMP, Campylobacter jejuni uses a novel thymidylate synthase, named ThyX (1). Different from canonical dimeric thymidylate synthase ThyA, ThyX is a flavoprotein and an active tetramer that utilizes NADPH as reducing agent, methylenetetrahydrofolate as methyl donor and dUMP as methyl acceptor. Its proposed catalytic mechanism starts with the oxidation of NADPH, followed by methylation of dUMP. ThyX proteins and human ThyA are unrelated in terms of sequence and structure, and use different catalytic mechanisms, making the essential ThyX enzymes interesting antimicrobial targets .